Production of nitrite by dengue virus-induced cytotoxic factor

Abstract

Dengue type 2 virus (DV) infection induces production of a cytokine, the cytotoxic factor (CF) in the spleen of mice. The present study was undertaken to investigate the production of nitrite (NO^-₂) by the spleen cells of mice in vitro and in vivo following inoculation of DV or CF. Maximum NO^-₂ production occurred at 45 min after inoculation of 5 μ g CF, both in vitro and in vivo. The NO^-₂ was produced by macrophages and T cells and not by B cells. Pretreatment of CF with anti-CF antisera inhibited production of NO^-₂. DV-stimulated spleen cell culture supernatants showed peak production of CF and NO^-₂ at 72 h. In DV-infected mouse spleen, maximum NO^-₂ production occurred at 8-11 days post-infection, which correlated with peak cytotoxic activity in the spleen. Pretreatment of spleen cells with N^G-monomethyl l-arginine (NMMA) inhibited NO^-₂ production. NO^-₂ production was abrogated in a dose-dependent manner by treatment of spleen cells with Ca²⁺ channel blocking drug, Nifedipine. The findings demonstrate that DV-induced CF induces production of NO^-₂ in spleen cells, probably in a Ca²⁺-dependent manner, and may be a mechanism of target cell killing.